Quantitative Parameters of Contrast-Enhanced Ultrasound Predicting the Response to Combined Immune Checkpoint Inhibitor and Anti-angiogenesis Therapies for Unresectable Hepatocellular Carcinoma

Ultrasound Med Biol. 2024 Mar;50(3):352-357. doi: 10.1016/j.ultrasmedbio.2023.11.005. Epub 2023 Dec 10.

Abstract

Objective: The aim of the work described here was to explore the value of contrast-enhanced ultrasound (CEUS) quantitative parameters in predicting the response of combined immune checkpoint inhibitor (ICI) and anti-angiogenesis therapies for unresectable hepatocellular carcinoma (HCC).

Methods: Sixty-six HCC patients who underwent combined ICI and anti-angiogenesis therapies were prospectively enrolled. A CEUS examination was performed at baseline, and tumor perfusion parameters were obtained with perfusion quantification software. The differences in CEUS quantitative parameters between the responder and non-responder groups were compared, and the correlations between CEUS parameters and progression-free survival (PFS) was evaluated.

Results: The objective response rate (ORR) was 21.2%. The values of rising time (RT) ratio, time to peak ratio, fall time ratio, peak enhancement ratio, wash-in rate ratio, wash-in perfusion index ratio and wash-out rate ratio differed significantly differed between the responder and non-responder groups (all p values < 0.05). Multivariable logistic regression analysis revealed that the RT ratio was the only independent factor associated with the ORR (odds ratio = 0.007, 95% confidence interval: 0.000-0.307, p = 0.010). The median RT ratios of the responder and non-responder groups were 36.9 and 58.9, respectively (p = 0.006). The appropriate cutoff point of the RT ratio was 80.1, determined with the X-tile program. Survival analysis indicated high PFS for the patients with a lower RT ratio (high RT ratio vs. low RT ratio = 4.4 mo vs. not reached, p = 0.001).

Conclusion: CEUS quantitative parameters may predict the efficacy of ICI and anti-angiogenesis combined therapies for HCC.

Keywords: Anti-angiogenesis; Contrast-enhanced ultrasound; Hepatocellular carcinoma; Immune checkpoint inhibitor; Quantitative analysis; Tumor response.

MeSH terms

  • Carcinoma, Hepatocellular* / diagnostic imaging
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / pathology
  • Contrast Media / therapeutic use
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy
  • Liver Neoplasms* / diagnostic imaging
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / pathology
  • Retrospective Studies
  • Ultrasonography

Substances

  • Immune Checkpoint Inhibitors
  • Contrast Media